Wogonin protects glomerular podocytes by targeting Bcl-2-mediated autophagy and apoptosis in diabetic kidney disease  

作　　者：Xue-qi Liu Ling Jiang Yuan-yuan Li Yue-bo Huang Xue-ru Hu Wei Zhu Xian Wang Yong-gui Wu Xiao-ming Meng Xiang-ming Qi 

机构地区：[1]Department of Nephropathy,The First Affiliated Hospital of Anhui Medical University,Hefei,230022,China [2]Center for Scientific Research of Anhui Medical University,Hefei,230022,China [3]The Key Laboratory of Major Autoimmune Diseases,Anhui Institute of Innovative Drugs,School of Pharmacy,Anhui Medical University,The Key Laboratory of Anti inflammatory and Immune Medicines,Ministry of Education,Hefei,230022,China

出　　处：《Acta Pharmacologica Sinica》2022年第1期96-110,共15页中国药理学报（英文版）

基　　金：The authors thank the Center for Scientific Research of Anhui Medical University for valuable help in our experiment.This study was supported by the Scientific Research Foundation of the Institute for Translational Medicine of Anhui Province(no.2017zhyx01);the Promotion Plan of Basic and Clinical Cooperative Research in Anhui Medical University(No.2019xkjT014);and Natural Science Research Project of Universities in Anhui Province(no.KJ2018A0493).

摘　　要：Diabetic kidney disease(DKD)is one of the microvascular complications of diabetes mellitus and a major cause of end-stage renal disease with limited treatment options.Wogonin is a flavonoid derived from the root of Scutellaria baicalensis Georgi,which has shown a potent renoprotective effect.But the mechanisms of action in DKD are not fully elucidated.In this study,we investigated the effects of wogonin on glomerular podocytes in DKD using mouse podocyte clone 5(MPC5)cells and diabetic mice model.MPC5 cells were treated with high glucose(30 mM).We showed that wogonin(4,8,16μM)dose-dependently alleviated high glucose(HG)-induced MPC5 cell damage,accompanied by increased expression of WT-1,nephrin,and podocin proteins,and decreased expression of TNF-α,MCP-1,IL-1βas well as phosphorylated p65.Furthermore,wogonin treatment significantly inhibited HG-induced apoptosis in MPC5 cells.Wogonin reversed HG-suppressed autophagy in MPC5 cells,evidenced by increased ATG7,LC3-II,and Beclin-1 protein,and decreased p62 protein.We demonstrated that wogonin directly bound to Bcl-2 in MPC5 cells.In HG-treated MPC5 cells,knockdown of Bcl-2 abolished the beneficial effects of wogonin,whereas overexpression of Bcl-2 mimicked the protective effects of wogonin.Interestingly,we found that the expression of Bcl-2 was significantly decreased in biopsy renal tissue of diabetic nephropathy patients.In vivo experiments were conducted in STZ-induced diabetic mice,which were administered wogonin(10,20,40 mg·kg^(−1)·d^(−1),i.g.)every other day for 12 weeks.We showed that wogonin administration significantly alleviated albuminuria,histopathological lesions,and p65 NF-κB-mediated renal inflammatory response.Wogonin administration dose-dependently inhibited podocyte apoptosis and promoted podocyte autophagy in STZ-induced diabetic mice.This study for the first time demonstrates a novel action of wogonin in mitigating glomerulopathy and podocytes injury by regulating Bcl-2-mediated crosstalk between autophagy and apoptosis.Wogonin may be a

关 键 词：diabetic kidney disease WOGONIN PODOCYTES AUTOPHAGY APOPTOSIS BCL-2 

分 类 号：R587.1[医药卫生—内分泌] R692[医药卫生—内科学] R96[医药卫生—临床医学]